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Objectives: To describe the distribution, consequences and potential determinants of time to antibiotics administration in children with community-onset severe bacterial infections (COSBIs)., Design: Secondary analysis of the available data from a prospective population-based study from 2009 to 2014., Setting: An administrative area in western France accounting for 13% of the national pediatric population., Patients: All children from 1 month to 16 years old admitted to a PICU or who died before admission and had a COSBI., Interventions: None., Measurements and Main Results: The time to antibiotics was divided into patient interval (from first signs of COSBI to the first medical consultation) and medical interval (from the first consultation to appropriate antibiotics administration). The association between the medical interval and child outcome was studied by a multinomial logistic regression model and the potential determinants of the patient and medical intervals were by a Cox proportional-hazards model. Of the 227 children included (median age 2.1 yr), 22 died (9.7%), and 21 (9.3%) had severe sequelae at PICU discharge. Median patient and medical intervals were 7.0 hours (interquartile range [IQR], 2.0-16.5 hr) and 3.3 hours (IQR, 1.1-12.2 hr), respectively. The last quartile of medical interval was not associated with death (adjusted odds ratio [aOR], 3.7; 95% CI, 0.8-17.5) or survival with severe sequelae (aOR, 1.3; 95% CI, 0.4-4.0) versus survival without severe sequelae. Patient interval was shorter in younger children (adjusted hazard ratio [aHR], 0.95; 95% CI, 0.92-0.99), and medical interval was reduced when the first consultation was conducted in a hospital (aHR, 1.5; 95% CI, 1.1-2.0) versus outpatient medicine., Conclusions: For children with COSBI, we found no significant association between medical interval and mortality or severe sequelae. An initial hospital referral could help reduce the time to antibiotics in COSBIs., Competing Interests: Dr. Malorey’s institution received funding from Direction générale de l’offre de soins—Ministère de la Santé et de la Prévention Français; he received funding from Société Française de Pédiatrie. Dr. Chalumeau received funding from Merck. Drs. Chantreuil, Martinot, and Gras-Le Guen received funding from Pfizer. Drs. Chantreuil and Martinot received funding from Sanofi, GlaxoSmithKline (GSK), and Merck. Dr. Chantreuil received funding from Eumedica, Correrio, and Biomerieux. Dr. Roue received funding from AbbVie and Chiesi. Dr. Martinot received funding from GSK. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Importance: Assessment of the quality of initial care is necessary to target priority actions that can reduce the still high morbidity and mortality due to community-onset severe bacterial infections (COSBIs) among children., Objective: To study the prevalence, characteristics, and determinants of suboptimal care in the initial management of COSBIs., Design, Setting, and Participants: This prospective, population-based, cohort study and confidential enquiry was conducted between August 2009 and January 2014 in western France, a region accounting for 15% of the French pediatric population (1 968 474 children aged 1 month to 16 years) and including 6 pediatric intensive care units (PICUs) and 35 emergency departments. Participants included all children aged 1 month to 16 years who died before PICU admission or were admitted to a PICU with a COSBI (ie, bacterial sepsis, including meningitis, purpura fulminans, and pulmonary, osteoarticular, intra-abdominal, cardiac, and soft-tissue severe infections). Data were analyzed from March to June 2020., Exposures: Suboptimal care determined according to evaluation of 8 types of care: (1) the delay in seeking care by family, (2) the physician's evaluation of severity, (3) the patient's referral at the first consultation with signs of severity, (4) the timing and (5) dosage of antibiotic treatment, (6) the timing and (7) volume of fluid bolus administration, and (8) the clinical reassessment after fluid bolus., Main Outcomes and Measures: Two experts assessed the quality of care before death or PICU admission as optimal, possibly suboptimal, or certainly suboptimal. The consequences and determinants of certainly suboptimal care were identified with multinomial logistic regression and generalized linear mixed models., Results: Of the 259 children included (median [IQR] age, 24 [6-66] months; 143 boys [55.2%]), 27 (10.4%) died, and 25 (9.6%) had severe sequelae at PICU discharge. The quality of care was certainly suboptimal in 89 cases (34.4%). Suboptimal care was more frequent in children with sequelae (adjusted odds ratio [aOR], 5.61; 95% CI, 1.19-26.36) and less frequent in children who died (aOR, 0.16; 95% CI, 0.04-0.65) vs those surviving without sequelae. Factors independently associated with suboptimal care were age younger than 5 years (aOR, 3.15; 95% CI, 1.25-7.90), diagnosis of sepsis with no source (aOR, 5.77; 95% CI, 1.64-20.30) or meningitis (aOR, 3.39; 95% CI, 1.15-9.96) vs other severe infections, and care by a primary care physician (aOR, 3.22; 95% CI, 1.17-8.88) vs a pediatric hospital service., Conclusions and Relevance: This study found that suboptimal care is frequent in the initial management of COSBI and is associated with severe sequelae. The paradoxical association with reduced risk of death may be explained by an insufficient adjustment on bacterial or host intrinsic factors. Management could be optimized by improving the quality of primary care, especially for young children.

Objectives: Diaphragmatic paralysis following congenital cardiac surgery is associated with significant morbidity and mortality. Spontaneous recovery of diaphragmatic function has been described, contrasting with centres providing early diaphragmatic plication. We aimed to describe the outcomes of a conservative approach, as well as to identify factors associated with a failure of the strategy., Methods: This is a retrospective study of patients admitted after cardiac surgery and suffering unilateral diaphragmatic paralysis within 2 French Paediatric Cardiac Surgery Centers. The conservative approach, defined by the prolonged use of ventilation until successful weaning from respiratory support, was the primary strategy adopted in both centres. In case of unsuccessful evolution, a diaphragmatic plication was scheduled. Total ventilation time included invasive and non-invasive ventilation. Diaphragm asymmetry was defined by the number of posterior rib segments counted between the 2 hemi-diaphragms on the chest X-ray after cardiac surgery., Results: Fifty-one neonates and infants were included in the analysis. Patients' median age was 12.0 days at cardiac surgery (5.0-82.0), and median weight was 3.5 kg (2.8-4.9). The conservative approach was successful for 32/51 patients (63%), whereas 19/51 patients (37%) needed diaphragm plication. There was no difference in patients' characteristics between groups. Respiratory support prolonged for 21 days or more and diaphragm asymmetry more than 2 rib segments were independently associated with the failure of the conservative strategy [odds ratio (OR) 6.9 (1.29-37.3); P = 0.024 and OR 6.0 (1.4-24.7); P = 0.013, respectively]., Conclusions: The conservative approach was successful for 63% of the patients. We identified risk factors associated with the strategy's failure., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: To describe the epidemiology of community-onset severe bacterial infections in children and its recent evolution., Design: Prospective, observational, population-based study from 2009 to 2014., Setting: An administrative area accounting for 13% of the French pediatric population., Patients: All children 1 month to 16 years old who died before admission or were admitted to a PICU for a community-onset severe bacterial infection., Interventions: None., Measurements and Main Results: The incidence and mortality rate of community-onset severe bacterial infections were compared with data from a reference population-based study conducted between 2000 and 2006, that is, before national recommendations for antimeningococcal C and antipneumococcal generalized vaccinations. Among the 261 children included (median age 25 mo), 28 (10.7%) died. The main diagnoses were meningitis (n = 85; 32%) and purpura fulminans (n = 59; 22%). The most common isolated bacteria were Neisseria meningitidis (n = 75; 29%), including 47 (63%) cases of serogroup B and 15 (20%) serogroup C, Streptococcus pneumoniae (n = 49, 19%), and Staphylococcus aureus (n = 15; 6%). The incidence of community-onset severe bacterial infections was three per 100,000 person-years (95% CI, 2.6-3.3) and had decreased by 53% from the reference period. Mortality rate was 0.3 per 100,000 person-years (95% CI, 0.2-0.4) and had decreased by 73% from the reference period. The incidence of community-onset severe bacterial infections caused by N. meningitidis and S. pneumoniae was 0.8 and 0.5 per 100,000 person-years and had decreased by 70% and 67% from the reference period. The incidence of community-onset severe bacterial infections-related to Staphylococcus aureus was 0.16 per 100,000 person-years and had increased by 220% from the reference period., Conclusions: The incidence and mortality rate of community-onset severe bacterial infections, except for S. aureus infection, have decreased in France. N. meningitidis and S. pneumoniae continue to account for many infections, which indicates the need for better vaccination coverage and spectrum.

Background: In a context of suboptimal vaccination coverage and increasing vaccine hesitancy, we aimed to study morbidity and mortality in children related to missing or incomplete meningococcal C and pneumococcal conjugate vaccines., Methods: We conducted a prospective, observational, population-based study from 2009 to 2014 in a French administrative area that included all children from age 1 month to 16 years who died before admission or were admitted to an intensive care unit for a community-onset bacterial infection. Vaccine-preventable infection was defined as an infection with an identified serotype included in the national vaccine schedule at the time of infection and occurring in a non- or incompletely vaccinated child. Death and severe sequelae were studied at hospital discharge. Frequencies of vaccine-preventable morbidity and mortality caused by meningococcus and pneumococcus were calculated., Results: Among the 124 children with serotyped meningococcal (n = 75) or pneumococcal (n = 49) severe infections included (median age 26 months), 20 (16%) died and 12 (10%) had severe sequelae. Vaccine-preventable infections accounted for 18/124 infections (15%, 95% CI 9, 22), 5/20 deaths (25%, 95% CI 9, 49), and 3/12 severe sequelae cases (25%, 95% CI 0, 54). The vaccine schedule for meningococcal C and pneumococcal conjugate vaccinations was incomplete for 71/116 (61%) children targeted by at least one of these two vaccination programs., Conclusions: Mortality and morbidity rates related to vaccine-preventable meningococcal or pneumococcal infection could be reduced by one quarter with better implementation of immunisation programs. Such information could help enhance the perception of vaccine benefits and fight vaccine hesitancy., (© 2018 John Wiley & Sons Ltd.)

Background: Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea cycle resulting in increased plasma levels of ammonia and glutamine and cerebral edema. However, the underlying mechanism of brain cytotoxicity remains controversial. Our objective is to present an unusual acute hyperammonemic crisis suggesting a key role of brain glutamine to mediate ammonia neurotoxicity and the interest of intracerebral pressure (ICP) monitoring to maintain adequate cerebral perfusion pressure and to prevent neurological damages., Patient: A 6-year-old boy with OTCD was admitted for an acute hyperammonemic encephalopathy following viral infection. At admission, he presented vomiting, confusion, lethargy (Glasgow scale 7/15), and bilateral papilledema, suggesting cerebral edema. Plasma ammonia level was slightly increased (194 μmol/L, rr 25-50 μmol/L), contrasting with the severity of neurological deterioration and with high levels of glutamine in plasma (1,949 μmol/L, rr 335-666 μmol/L) and the brain (10-fold increase on in vivo MR spectroscopy). The patient was placed on neuroprotective treatments and respiratory support., Main Results: With a hypercaloric protein-free diet and nitrogen scavenger drugs, plasma levels of ammonia and glutamine rapidly decreased without neurological improvement. Continuous ICP monitoring showed repetitive peaks of pressure up to 60 mmHg in the first four days and was helpful to manage neuroprotective treatments. After several days, the patient progressively recovered without cognitive or motor disability., Conclusion: This case report highlights the discrepancy between the severity of neurological impairment, presumably related to high level of brain glutamine, and plasma levels of ammonia or glutamine in a child with acute hyperammonemic encephalopathy related to OTCD. In this situation, continuous ICP monitoring was helpful to manage neuroprotective treatments and prevent brain damages.

Background: Morbidity and mortality are higher for cardiac reoperations than first operation due to the presence of post-operative adhesions. We retrospectively evaluated the efficacy of the bioresorbable membrane Seprafilm to prevent pericardial adhesions after cardiac surgery in a paediatric congenital heart disease population., Methods: Seventy-one children undergoing reoperations with sternotomy redo and cardiopulmonary bypass for congenital malformations were included. Twenty-nine of these patients were reoperated after previous application of Seprafilm (treatment group). The duration of dissection, aortic cross clamping and total surgery were recorded. A tenacity score was established for each intervention from the surgeon's description in the operating report., Results: In multivariate analysis, the duration of dissection and the tenacity score were lower in the treatment than control group (p < 0.01), independent of age and interval since preceding surgery., Conclusion: Our results suggest that Seprafilm is effective in reducing the post-operative adhesions associated with infant cardiac surgery. We recommend the use of Seprafilm in paediatric cardiac surgery when staged surgical interventions are necessary.

Case Report: Malignant pertussis is a critical clinical state associated with fatal outcome in 70% of cases. The severity criteria are a lung infection with pulmonary hypertension and hyperleukocytosis usually above 50 G/L. We report the case of a 2.5-month-old girl hospitalized with critical pertussis in a pediatric intensive care unit. She had acute respiratory distress syndrome with pulmonary hypertension complicated by a bacterial secondary infection with Enterobacter cloacae managed by high-frequency oscillatory ventilation associated with pulmonary vasodilatation therapy. In the absence of clinical improvement and before considering extracorporeal life support, exchange transfusion was performed at day 9 to reduce hyperleukocytosis at 70 G/L. Exchange transfusion was successfully performed with a reduction of leukocytes to under 40 G/L followed by steady improvement of pulmonary function. Weaning from mechanical ventilation and discharge took place at day 23 and 38, respectively., Comments: Exchange transfusion should be considered in infants suffering from malignant pertussis with extreme leukocytosis before hemodynamic failure to improve the survival prognosis., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

We report the case of a 3-month-old boy hospitalized with acute bronchiolitis. Respiratory distress was associated with cardiogenic shock caused by chaotic atrial tachycardia. The cause of bronchiolitis was a coronavirus NL63 viral infection, confirmed in nasopharyngeal aspirations. The patient required intensive care including diuretics (furosemide), anti-arrhythmic drugs (amiodarone and digoxin), and inotropic drugs (milrinone and levosimendan) associated with mechanical ventilation. The outcome was favorable in 10 days and the sinusal cardiac rhythm was completely restored at discharge., (Copyright © 2013. Published by Elsevier SAS.)

Pompe disease is an autosomal recessive glycogen storage disorder caused by acid-alpha-glucosidase deficiency. The infantile form is usually fatal by 1 year of age in the absence of specific therapy. We report the cardiac follow-up of a 4-month-old boy treated with enzyme replacement therapy (ERT) for 8 months. The patient had no cardiac failure at the age of 1 year. Before starting ERT, ECG showed a shortened PR interval, with huge QRS complexes and biventricular hypertrophy; echocardiography demonstrated major hypertrophic cardiomyopathy. The QRS voltage (SV1+RV6) decreased from 13 to 2.9 mV after 32 weeks of ERT, suggesting a progressive reduction of cardiac hypertrophy and intracellular glycogen excess. The PR interval increased from 60 to 90 ms. A block of the right bundle branch appeared after 13 weeks of treatment. The indexed left ventricular mass decreased from 240 to 90 g/m2 after 30 weeks of ERT. The left ventricular ejection fraction decreased transitorily between the 5th and the 15 th weeks of treatment. In summary, ERT is an efficient therapeutic approach for the cardiomyopathy of infantile Pompe disease. However, the possible occurrence of a right bundle branch block and a transitory alteration in the ejection fraction highlight the importance of cardiac follow-up.

The biosynthesis of prostaglandins E2 (PGE2) and F2 alpha (PGF2) from exogenous arachidonic acid (AA) was investigated in 12 involved and uninvolved psoriatic epidermis and in 6 normal epidermis. PGE2 and PGF2 were determined by radio-immuno-assay after addition of 25 microgram of AA and 1 hour incubation. The biosynthesis of PGE2 and PGF2 alpha was higher in psoriatic epidermis than in control epidermis but lower in involved than in uninvolved epidermis. The ratio PGE2/PGF2 alpha is decreased in involved epidermis when compared with uninvolved epidermis and with controls. These quantitative and qualitative disturbances of the PG metabolism in psoriatic epidermis might play an important role in the pathogenesis of the disease. They could be responsible for abnormal keratinocyte differentiation and proliferation, lipid membrane abnormalities and abnormal immune response of psoriatic patients.